TY - JOUR

T1 - Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy

AU - Brignone, Juan

AU - Jensen, Mia

AU - Jensen, Boye L.

AU - Assersen, Kasper Bostlund

AU - Goetze, Jens P.

AU - Jodal, Lars

AU - Andersen, Trine Borup

AU - Magnusdottir, Sigridur Olga

AU - Kloster, Brian

AU - Jonler, Morten

AU - Lund, Lars

PY - 2023

Y1 - 2023

N2 - Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 +/- 6 mL/min, left 31 +/- 7 mL/min) accounted for the total GFR (56 +/- 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 +/- 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

AB - Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 +/- 6 mL/min, left 31 +/- 7 mL/min) accounted for the total GFR (56 +/- 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 +/- 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

KW - acute kidney injury

KW - albuminuria

KW - GFR

KW - natriuretic peptides

KW - partial nephrectomy

KW - ATRIAL-NATRIURETIC-PEPTIDE

KW - RECEPTOR

KW - ISCHEMIA

U2 - 10.1093/ndt/gfac200

DO - 10.1093/ndt/gfac200

M3 - Journal article

C2 - 35704678

VL - 38

SP - 80

EP - 92

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 1

ER -